. Hematopoietic stem cell are the ideal target for gene therapy of a variety of inherited and other disorders of the hematopoietic system. Administration of therapeutic genes to hematopoietic stem cells will provide a more robust treatment for disease than the introduction of genes into the progeny of cell types that are affected. To target gene delivery to hematopoietic stem cells, the investigators propose to develop a non-viral DNA delivery system capable of transferring DNA to human hematopoietic stem cells. The system uses a fusion protein that contains an antibody moiety directed against the hematopoietic stem cell specific surface marker CD34 and a DNA binding moiety. Four human anti-CD34 antibodies have been cloned as Fab genes, and will be used to synthesize fusion proteins with the human DNA binding protein protamine. This will be used to deliver plasmids containing marker genes to CD34-expressing cells. The ultimate goal is to develop a gene delivery vehicle that can be administered to patients in vivo. In this proposal, genes encoding fusion proteins will be synthesized, the protein will be expressed in sufficient quantities to test efficacy in cell culture, and gene delivery will be evaluated in cultured and primary CD34+ cells.